SAN FRANCISCO -- Heart rate and anticoagulation control may contribute to the relationship between atrial fibrillation and dementia, two studies showed.

Action Points

Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that these observational studies suggest a link between therapeutic anticoagulation and a decreased risk of dementia in those with atrial fibrillation.

Be aware that difficulty maintaining therapeutic anticoagulation may be associated with other, unmeasured risk factors including poor health behaviors.

SAN FRANCISCO -- Heart rate and anticoagulation control may contribute to the relationship between atrial fibrillation and dementia, two studies showed.

In one study, warfarin-treated patients with the greatest time spent within the therapeutic range were significantly less likely to develop dementia over at least 5 years of follow-up. And in the other, patients with higher average heart rates tended to have lower risks of dementia.

"We're starting to uncover the links between atrial fibrillation and dementia and we've learned that -- as we've anticipated -- it's probably multifactorial," Bunch told MedPage Today, adding that the findings suggest that dementia risk could be mitigated by more aggressively managing anticoagulation or by maintaining heart rate at a higher level.

Bunch and his colleagues explored anticoagulation control as a possible mechanism linking atrial fibrillation and dementia based on the idea that under-coagulation might result in microemboli and over-coagulation might result in microbleeds, both of which might damage the brain and eventually lead to dementia.

The analysis included 2,693 patients with atrial fibrillation treated with warfarin at the Intermountain anticoagulation clinic. The average age of the patients was 74. Through at least 5 years of follow-up, 4% of the patients developed some type of dementia.

The risk of developing dementia was significantly elevated for those who were in the therapeutic range (an international normalized ratio [INR] of 2 to 3) 75% of the time or less versus those who were were in the therapeutic range more than 75% of the time:

Less than 25% of the time (HR about 4.0, P<0.0001)

25% to 50% of the time (HR about 3.5, P<0.0001)

51% to 75% of the time (HR about 2.0, P=0.001)

There was a U-shaped curve, Bunch said, such that having an INR either below 2.0 or above 3.0 was associated with increased risks of dementia.

"So it appears that at least one of the mechanisms [linking atrial fibrillation and dementia] is chronic ischemic injury to the brain either from microembolism or microbleeds," he said.

"I think the goods news is that it suggests a way that we can minimize dementia in the sense that if we carefully control anticoagulation it reduces risk, or perhaps if we use some of these newer agents that are much easier to control, the dementia risk decreases," he said.

"The bad news is that there is a risk of dementia over time with anticoagulation use," he continued. "This may be a pervasive risk with all anticoagulants, and so that may suggest that we need to start looking at strategies that are independent of long-term drug need, such as these left atrial appendage closure devices."

The second study included information from 1,071 patients who underwent 24-hour Holter monitoring and had continuous atrial fibrillation and was based on the idea that heart rate can affect cerebral perfusion.

Through about 3 years of follow-up, the researchers found that patients with higher average heart rates tended to have lower risks of dementia:

Less than 60 beats per minute: 3%

60 to 79 bpm: 3.6%

80 to 99 bpm: 2.3%

100 bpm or higher: 0.8%

After multivariate adjustment, the hazard ratios for dementia associated with the three lowest categories of heart rate all indicated an increased risk relative to the highest heart rates -- HRs of 3.52, 4.20, and 2.46, respectively -- although the lower end of the 95% confidence interval crossed 1.00 for all of them, indicating nonsignificant differences.

Bunch noted that in recent years there has been a move toward more lenient control of heart rate in patients with atrial fibrillation, pointing to a recent trial showing that stricter control of heart rate did not improve outcomes versus more lenient control.

The current study "is just another part of that puzzle where we can see even on a cerebral functioning level that the body does better with allowing the heart rate to be somewhat higher, which I think allows for better organ perfusion," Bunch said. "It gives more supportive evidence to be not quite as aggressive with heart rate control strategies."

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